Ignite Creation Date:
2024-05-05 @ 10:59 PM
Last Modification Date:
2024-10-26 @ 10:26 AM
Study NCT ID:
NCT01225679
Status:
COMPLETED
Last Update Posted:
2014-02-06
First Post:
2010-07-07
Brief Title:
Late-onset Congenital Central Hypoventilation Syndrome and the Mutation of Phox2B Gene
Sponsor:
Associação Fundo de Incentivo à Pesquisa
Organization:
Associação Fundo de Incentivo à Pesquisa
Study Overview
Official Title:
Late-onset Insidious Course and Invasive Treatment of Congenital Central Hypoventilation Syndrome in a Case With the Phox2B Mutation
Status:
COMPLETED
Status Verified Date:
2014-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CCHS
Brief Summary:
Congenital central hypoventilation syndrome CCHS is a rare disorder of respiratory control characterized by ventilatory impairment that results in arterial hypoxemia Although patients typically present this disease as newborns and rarely in later infancy there have been reports of patients presenting with CCHS in adulthood
The present study reports a unique familial case in which the father proband presented late-onset CCHS with an expansion mutation of the Phox2B gene that was confirmed by genetic analysis Surprisingly the proband did not report any manifestation of the disease during childhood and the disease progressed following an insidious course until adulthood At the time of diagnosis he did not present signs of pulmonary hypertension and right-side heart failure The patient responded well to nocturnal invasive ventilation In contrast his son presented CCHS as a newborn with the full complement of symptoms while his daughter did not
The present report shows that CCHS cases characterized by a mutated Phox2 gene can progress without many symptoms and that the treatment approach used here was efficient for controlling the course of the disease Furthermore this case indicates that incomplete penetrance can occur Genetic screening of family members is mandatory to evaluate the reproductive risk of the disease especially because asymptomatic mutation carriers may be at high risk to develop the disease and transmit it to the next generation
The present study reports a unique familial case in which the father proband presented late-onset CCHS with an expansion mutation of the Phox2B gene that was confirmed by genetic analysis Surprisingly the proband did not report any manifestation of the disease during childhood and the disease progressed following an insidious course until adulthood At the time of diagnosis he did not present signs of pulmonary hypertension and right-side heart failure The patient responded well to nocturnal invasive ventilation In contrast his son presented CCHS as a newborn with the full complement of symptoms while his daughter did not
The present report shows that CCHS cases characterized by a mutated Phox2 gene can progress without many symptoms and that the treatment approach used here was efficient for controlling the course of the disease Furthermore this case indicates that incomplete penetrance can occur Genetic screening of family members is mandatory to evaluate the reproductive risk of the disease especially because asymptomatic mutation carriers may be at high risk to develop the disease and transmit it to the next generation
Detailed Description:
Congenital central hypoventilation syndrome CCHS is a rare disorder of respiratory control characterized by ventilatory impairment that results in arterial hypoxemia This condition worse during sleep and occurs in patients with normal mechanical properties of the lung It is diagnosed in the absence of primary neuromuscular disease identifiable brainstem lesions and other sleep disturbances or substance use
Amiel et al 2003 identified a mutation in the Phox2B gene associated with CCHS characterized by 5 to 9 alanine expansions within a 20-residue polyalanine region in exon 3 of the Phox2B gene Several reports confirmed the findings of Amiel et al supporting the view that this gene is a master switch for the development of the autonomic nervous system network linked to respiratory control Transgenic animals carrying the human Phox2B mutation develop a similar phenotype and lack glutamatergic neurons located in the parafacial region in the brainstem which are involved in breathing control
Although patients typically present with CCHS as newborns and rarely in later infancy there have been reports of patients presenting with CCHS in adulthood In cases of late-onset CCHS most patients report having had some symptoms since childhood and they have parents with a history of CCHS Symptoms of right-side heart failure are generally observed at the time of diagnosis and nocturnal noninvasive ventilation is frequently indicated
The present study reports a unique familial case of CCHS in which the father proband presented late-onset CCHS linked to a Phox2B gene expansion mutation The presentation course of development and treatment response for this patient was unique His son presented CCHS as a newborn while his daughter did not
Amiel et al 2003 identified a mutation in the Phox2B gene associated with CCHS characterized by 5 to 9 alanine expansions within a 20-residue polyalanine region in exon 3 of the Phox2B gene Several reports confirmed the findings of Amiel et al supporting the view that this gene is a master switch for the development of the autonomic nervous system network linked to respiratory control Transgenic animals carrying the human Phox2B mutation develop a similar phenotype and lack glutamatergic neurons located in the parafacial region in the brainstem which are involved in breathing control
Although patients typically present with CCHS as newborns and rarely in later infancy there have been reports of patients presenting with CCHS in adulthood In cases of late-onset CCHS most patients report having had some symptoms since childhood and they have parents with a history of CCHS Symptoms of right-side heart failure are generally observed at the time of diagnosis and nocturnal noninvasive ventilation is frequently indicated
The present study reports a unique familial case of CCHS in which the father proband presented late-onset CCHS linked to a Phox2B gene expansion mutation The presentation course of development and treatment response for this patient was unique His son presented CCHS as a newborn while his daughter did not
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None